Molluscum contagiosum virus (MCV) is a human poxvirus that causes asymptomatic cutaneous neoplasms that can persist for months to years in the skin of healthy or immunodeficient individuals, particularly children. Persistent infections with this virus are increasing and have become troublesome complications for adults with AIDS. At present there is no specific preventive or treatment for the disease. All attempts to culture the virus have failed and little is known about it. The objectives of the project are to analyze the structure of the viral genome, identify its genes, determine its mode of expression and replication, and find potential therapeutic targets. The way the virus resists the human immune system is of particular interest. In previous years, we succeeded in sequencing the entire genome of MCV and presently we are analyzing the functions of several interesting genes. Selenium, an essential trace element, is a component of prokaryotic and eukaryotic antioxidant proteins. A candidate selenoprotein homologous to glutathione peroxidase was deduced from the sequence of MCV. Selenium was incorporated into this protein during biosynthesis, and a characteristic stem-loop structure near the end of the messenger RNA was required for alternative selenocysteine decoding of a potential UGA stop codon within the open reading frame. The selenoprotein protected human keratinocytes against cytotoxic effects of ultraviolet irradiation and hydrogen peroxide, providing a mechanism for a virus to defend itself against environmental stress. A secreted CC chemokine homolog, encoded by MCV, potently interfered with the chemotaxis of human monocytes, lymphocytes, and neutrophils in response to a large number of CC and CXC chemokines with diverse receptor specificities. Evidence that the viral protein binds to human chemokine receptors was obtained by competition binding and calcium mobilization experiments. The broad spectrum chemokine antagonistic activity of this MCV protein can explain the prolonged absence of an inflammatory response in skin tumors that harbor replicating MCV.